{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:08:35Z","timestamp":1790071715564,"version":"4.0.1"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    Post-stroke cognitive impairment (PSCI) is a common and debilitating neurological complication following cerebral ischemia\u2013reperfusion injury (CIRI). The traditional neuron-centered view cannot fully explain its delayed onset, pathological heterogeneity, and functional plasticity. This review proposes a novel neuroecosystem framework based on the neurovascular-immune-glial (NIG) triad, including a systematic evaluation of the dynamic crosstalk among the neurovascular unit (NVU), neuronal networks, and glial-immune microenvironment. Pathological events, including ferroptosis, neuroinflammation, white matter damage, and gut-brain axis dysfunction, are reinterpreted as manifestations of neuroecosystem collapse, rather than isolated lesions. We further summarize cutting-edge tools, such as spatial omics and\n                    <jats:italic>in vivo<\/jats:italic>\n                    dynamic imaging for framework validation, and clarify how therapeutic strategies are shifting from single neuronal protection to overall ecosystem restoration. Finally, we discuss current limitations in knowledge and future research directions, aiming to provide new insights for mechanistic exploration and clinical intervention of PSCI.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2026.1912737","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:40:58Z","timestamp":1790070058000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cognitive impairment after cerebral ischemia\u2013reperfusion injury: a neuroecosystem perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiangbo","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Neurology, Weifang Hospital of Traditional Chinese Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Fujian Medical University","place":["Fuzhou, China"]},{"name":"Department of Rehabilitation, Weifang Hospital of Traditional Chinese Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Weifang Hospital of Traditional Chinese Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Integration of Traditional Chinese and Western Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weifang Hospital of Traditional Chinese Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weifang Hospital of Traditional Chinese Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1562925","DOI":"10.3389\/fnagi.2025.1562925","article-title":"Neuroprotective effects of electroacupuncture in ischemic stroke: from mechanisms to clinical implications","volume":"17","author":"Zhu","year":"2025","journal-title":"Front Aging Neurosci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"109900","DOI":"10.1016\/j.cbi.2022.109900","article-title":"MiR-203a-3p\/153-3p improves cognitive impairments induced by ischemia\/reperfusion via blockade of SRC-mediated MAPK signaling pathway","volume":"358","author":"Li","year":"2022","journal-title":"Chem Biol Interact"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"215","DOI":"10.5114\/fn.2024.134300","article-title":"Ginsenoside Rb1 attenuates mouse cerebral ischemia\/reperfusion induced neurological impairments through modulation of microglial polarization","volume":"62","author":"Yu","year":"2024","journal-title":"Folia Neuropathol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3390\/biomedicines12092077","article-title":"Effects of sildenafil on cognitive function recovery and neuronal cell death protection after transient global cerebral ischemia","volume":"12","author":"Yu","year":"2024","journal-title":"Biomedicine"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1007\/s11064-022-03575-3","article-title":"Electroacupuncture ameliorates cognitive impairment through the inhibition of NLRP3 inflammasome by regulating mitophagy","volume":"47","author":"Zhong","year":"2022","journal-title":"Neurochem Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"0262","DOI":"10.34133\/cbsystems.0262","article-title":"Accelerated molecular transportation in the brain extracellular space attenuates post-stroke cognitive impairment","volume":"6","author":"Yang","year":"2025","journal-title":"Cyborg Bionic Syst"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"682908","DOI":"10.3389\/fnagi.2021.682908","article-title":"Carotid atherosclerotic calcification characteristics relate to post-stroke cognitive impairment","volume":"13","author":"Wang","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"804","DOI":"10.2174\/011570159X440842251020104840","article-title":"Emerging potential of Ras-proximate-1 in mediating neurodegenerative diseases","volume":"24","author":"Wang","year":"2025","journal-title":"Curr Neuropharmacol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.1002\/glia.23875","article-title":"Tightening the retinal glia limitans attenuates neuroinflammation after optic nerve injury","volume":"68","author":"Lefevere","year":"2020","journal-title":"Glia"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e13164","DOI":"10.1111\/bpa.13164","article-title":"Monomeric C-reactive protein: a novel biomarker predicting neurodegenerative disease and vascular dysfunction","volume":"33","author":"Pastorello","year":"2023","journal-title":"Brain Pathol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"13556","DOI":"10.1038\/s41598-025-96952-1","article-title":"Serum neurofilament heavy chain predicts post-stroke cognitive impairment","volume":"15","author":"Qiao","year":"2025","journal-title":"Sci Rep"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"863","DOI":"10.4103\/1673-5374.353494","article-title":"DNA hypomethylation promotes learning and memory recovery in a rat model of cerebral ischemia\/reperfusion injury","volume":"18","author":"Shi","year":"2023","journal-title":"Neural Regen Res"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"4616","DOI":"10.7150\/thno.54210","article-title":"Decreased neuronal synaptosome associated protein 29 contributes to poststroke cognitive impairment by disrupting presynaptic maintenance","volume":"11","author":"Yan","year":"2021","journal-title":"Theranostics"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"125329","DOI":"10.1016\/j.ijpharm.2025.125329","article-title":"Macrophage membrane coated functionalized nanoparticles for targeted drug delivery and neural function repair in cerebral ischemia-reperfusion injury","volume":"672","author":"Li","year":"2025","journal-title":"Int J Pharm"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3390\/brainsci14060614","article-title":"Transcranial direct current stimulation to ameliorate post-stroke cognitive impairment","volume":"14","author":"Sloane","year":"2024","journal-title":"Brain Sci"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"7134","DOI":"10.1002\/jcp.30357","article-title":"The region-selective regulation of endothelial claudin-5 expression and signaling in brain health and disorders","volume":"236","author":"Chiba","year":"2021","journal-title":"J Cell Physiol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3892\/br.2025.1966","article-title":"Research developments in the neurovascular unit and the blood-brain barrier (review)","volume":"22","author":"Gong","year":"2025","journal-title":"Biomed Rep"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"575598","DOI":"10.3389\/fphys.2020.575598","article-title":"Increased immunosignals of collagen IV and fibronectin indicate ischemic consequences for the neurovascular matrix adhesion zone in various animal models and human stroke tissue","volume":"11","author":"Michalski","year":"2020","journal-title":"Front Physiol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"114942","DOI":"10.1016\/j.expneurol.2024.114942","article-title":"In vitro modelling of the neurovascular unit for ischemic stroke research: emphasis on human cell applications and 3D model design","volume":"381","author":"Pang","year":"2024","journal-title":"Exp Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"866700","DOI":"10.3389\/fnmol.2022.866700","article-title":"The role of pericytes in ischemic stroke: from cellular functions to therapeutic targets","volume":"15","author":"Zhou","year":"2022","journal-title":"Front Mol Neurosci"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e12671","DOI":"10.1111\/micc.12671","article-title":"The cerebral microvasculature: basic and clinical perspectives on stroke and glioma","volume":"28","author":"Hoque","year":"2021","journal-title":"Microcirculation"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"833431","DOI":"10.3389\/fnagi.2022.833431","article-title":"The important double-edged role of astrocytes in neurovascular unit after ischemic stroke","volume":"14","author":"Han","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"22065","DOI":"10.1021\/acsnano.5c02105","article-title":"Inflammatory oriented nanospheres-reconstructed extracellular matrix in ischemic stroke","volume":"19","author":"Gao","year":"2025","journal-title":"ACS Nano"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1177\/0271678X20951995","article-title":"Regulation of blood-brain barrier integrity by microglia in health and disease: a therapeutic opportunity","volume":"40","author":"Ronaldson","year":"2020","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"8104","DOI":"10.1007\/s12035-024-04092-w","article-title":"Involvement of calpain in neurovascular unit damage through up-regulating PARP-NF-\u03baB signaling during experimental ischemic stroke","volume":"61","author":"Yan","year":"2024","journal-title":"Mol Neurobiol"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207554","article-title":"Roadmap for stroke: challenging the role of the neuronal extracellular matrix","volume":"21","author":"De Luca","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e12940","DOI":"10.1111\/bpa.12940","article-title":"Reconstituting neurovascular unit with primary neural stem cells and brain microvascular endothelial cells in three-dimensional matrix","volume":"31","author":"Wang","year":"2021","journal-title":"Brain Pathol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"111647","DOI":"10.1016\/j.brainresbull.2025.111647","article-title":"Multifunctionality of tissue inhibitor of metalloproteinase-1 in central nervous system diseases","volume":"233","author":"Zhong","year":"2025","journal-title":"Brain Res Bull"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041539","article-title":"Neurons glia, extracellular matrix and neurovascular unit: a systems biology approach to the complexity of synaptic plasticity in health and disease","volume":"21","author":"De Luca","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2316","DOI":"10.1111\/jnc.16106","article-title":"Infiltration of immune cells to the brain and its relation to the pathogenesis of Alzheimer's and Parkinson's diseases","volume":"168","author":"Netzahualcoyotzi","year":"2024","journal-title":"J Neurochem"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"662","DOI":"10.3724\/zdxbyxb-2023-0144","article-title":"Research progress on the roles of neurovascular unit in stroke-induced immunosuppression","volume":"52","author":"Zhou","year":"2023","journal-title":"J Zhejiang Univ (Med Sci)"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/978-1-0716-4706-6_4","article-title":"A guided approach to establish a functional humanized brain-on-a-chip microfluidic model of the neurovascular system","volume":"2956","author":"Raut","year":"2025","journal-title":"Methods Mol Biol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e2300004","DOI":"10.1002\/adhm.202300004","article-title":"3D bioprinting of neurovascular tissue modeling with collagen-based low-viscosity composites","volume":"12","author":"Wang","year":"2023","journal-title":"Adv Healthc Mater"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"IMAG-a","DOI":"10.1162\/IMAG.a.77","article-title":"Linking neuron-axon-synapse architecture to white matter vasculature using high-resolution multimodal MRI in primate brain","volume":"3","author":"Kimura","year":"2025","journal-title":"Imaging Neurosci"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"498","DOI":"10.3171\/2023.6.JNS232","article-title":"Bilateral brain microstructural alterations in patients with left-sided classic trigeminal neuralgia: a diffusion kurtosis imaging study","volume":"140","author":"Xiong","year":"2024","journal-title":"J Neurosurg"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.ajhg.2022.01.004","article-title":"Bi-allelic variants in neuronal cell adhesion molecule cause a neurodevelopmental disorder characterized by developmental delay hypotonia, neuropathy\/spasticity","volume":"109","author":"Kurolap","year":"2022","journal-title":"Am J Hum Genet"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1566155","DOI":"10.3389\/fpsyt.2025.1566155","article-title":"Genetic association between gene expression profiles in oligodendrocyte precursor cells and psychiatric disorders","volume":"16","author":"Kondo","year":"2025","journal-title":"Front Psych"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1038\/s42003-025-08177-7","article-title":"White matter dysfunction in Alzheimer's disease is associated with disease-related transcriptomic signatures","volume":"8","author":"Li","year":"2025","journal-title":"Commun Biol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"586321","DOI":"10.3389\/fnins.2020.586321","article-title":"Levodopa improves cognitive function and the deficits of structural synaptic plasticity in hippocampus induced by global cerebral ischemia\/reperfusion injury","volume":"14","author":"Wang","year":"2020","journal-title":"Front Neurosci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e1449242024","DOI":"10.1523\/JNEUROSCI.1449-24.2024","article-title":"Abnormal local cortical functional connectivity due to interneuron dysmaturation after neonatal intermittent hypoxia","volume":"45","author":"Goussakov","year":"2025","journal-title":"J Neurosci"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1088\/1741-2552\/ad0e7c","article-title":"Towards an optimised deep brain stimulation using a large-scale computational network and realistic volume conductor model","volume":"20","author":"Spiliotis","year":"2024","journal-title":"J Neural Eng"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.4103\/1673-5374.367832","article-title":"Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease","volume":"18","author":"Yue","year":"2023","journal-title":"Neural Regen Res"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1015556","DOI":"10.3389\/fncel.2022.1015556","article-title":"The implication of a diversity of non-neuronal cells in disorders affecting brain networks","volume":"16","author":"Carrier","year":"2022","journal-title":"Front Cell Neurosci"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"105949","DOI":"10.1016\/j.neuint.2025.105949","article-title":"Research progress on the mechanisms of microglial extracellular vesicles affecting the prognosis of ischemic stroke","volume":"185","author":"An","year":"2025","journal-title":"Neurochem Int"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"653334","DOI":"10.3389\/fnagi.2021.653334","article-title":"Role of neuron and glia in Alzheimer's disease and associated vascular dysfunction","volume":"13","author":"Bandyopadhyay","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"692061","DOI":"10.3389\/fimmu.2021.692061","article-title":"New insight into neutrophils: a potential therapeutic target for cerebral ischemia","volume":"12","author":"Chen","year":"2021","journal-title":"Front Immunol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"102700","DOI":"10.1016\/j.tube.2025.102700","article-title":"The cytokine profiles of the inflammatory response in chronic granulomatous encephalitis caused by Mycobacterium tuberculosis do not influence the patient's clinical presentation","volume":"155","author":"Rivas-Castro","year":"2025","journal-title":"Tuberculosis"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"eadg1656","DOI":"10.1126\/scitranslmed.adg1656","article-title":"Gut-licensed \u03b27+ CD4+ T cells contribute to progressive retinal ganglion cell damage in glaucoma","volume":"15","author":"He","year":"2023","journal-title":"Sci Transl Med"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13064-024-00195-1","article-title":"Mapping the cellular expression patterns of vascular endothelial growth factor aa and bb genes and their receptors in the adult zebrafish brain during constitutive and regenerative neurogenesis","volume":"19","author":"Fernezelian","year":"2024","journal-title":"Neural Dev"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1042\/BST20230329","article-title":"Endothelial neuropilin-1: a multifaced signal transducer with an emerging role in inflammation and atherosclerosis beyond angiogenesis","volume":"52","author":"Chikh","year":"2024","journal-title":"Biochem Soc Trans"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/s12974-025-03475-7","article-title":"Chemokine-complement cascade in glial-vascular units protects neurons from non-biogenic nanoparticles","volume":"22","author":"Ogaki","year":"2025","journal-title":"J Neuroinflammation"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"110236","DOI":"10.1016\/j.exer.2025.110236","article-title":"miRNAs piRNAs, and lncRNAs: a triad of non-coding RNAs regulating the neurovascular unit in diabetic retinopathy and their therapeutic potentials","volume":"251","author":"Karpagavalli","year":"2025","journal-title":"Exp Eye Res"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1177\/0271678x20985156","article-title":"Imaging biomarkers of vascular and axonal injury are spatially distinct in chronic traumatic brain injury","volume":"41","author":"Haber","year":"2021","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.jare.2025.05.047","article-title":"In newly diagnosed diabetes, hyperglycemia is associated with increased brain iron deposition, measured by MRI-based quantitative susceptibility mapping (QSM)","volume":"81","author":"Pirozzi","year":"2025","journal-title":"J Adv Res"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1002\/jmri.70432","article-title":"Association between deep gray matter iron deposition dysregulation and cognitive performance in type 2 diabetes mellitus patients: a quantitative susceptibility mapping study","volume":"63","author":"Wang","year":"2026","journal-title":"J Magn Reson Imaging"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1123456","DOI":"10.3389\/fnins.2023.1061156","article-title":"Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus","volume":"17","author":"Hu","year":"2023","journal-title":"Front Neurosci"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1007\/s12035-026-05704-3","article-title":"Ptbp2 alleviates neuroinflammation and blood-brain barrier disruption via modulating microglial polarization in ischemic stroke","volume":"63","author":"Xu","year":"2026","journal-title":"Mol Neurobiol"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1161\/STROKEAHA.107.500868","article-title":"MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke","volume":"39","author":"Rosell","year":"2008","journal-title":"Stroke"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"271678X261479277","DOI":"10.1177\/0271678X261479277","article-title":"Immunothrombosis may drive futile reperfusion in stroke","volume":"46","author":"Shu","year":"2026","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1161\/STROKEAHA.117.017080","article-title":"Exacerbation of thromboinflammation by hyperglycemia precipitates cerebral infarct growth and hemorrhagic transformation","volume":"48","author":"Desilles","year":"2017","journal-title":"Stroke"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1146\/annurev-cancerbio-030518-055844","article-title":"The hallmarks of ferroptosis: an emerging cell death pathway in disease","volume":"3","author":"Dixon","year":"2019","journal-title":"Annu Rev Cancer Biol"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.tcb.2015.10.014","article-title":"Ferroptosis: death by lipid peroxidation","volume":"26","author":"Yang","year":"2016","journal-title":"Trends Cell Biol"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.fmre.2021.07.008","article-title":"Generation of singlet oxygen via iron-dependent lipid peroxidation and its role in ferroptosis","volume":"2","author":"Zhang","year":"2022","journal-title":"Fundam Res"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1038\/s41418-026-01692-y","article-title":"ACSL4-mediated astrocyte ferroptosis augments neuroinflammation and exacerbates NMOSD pathology","volume":"33","author":"Wen","year":"2026","journal-title":"Cell Death Differ"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1053\/gast.2001.24033","article-title":"Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload","volume":"120","author":"Zoller","year":"2001","journal-title":"Gastroenterology"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"110778","DOI":"10.1016\/j.brainresbull.2023.110778","article-title":"Enriched environment attenuates ferroptosis after cerebral ischemia\/reperfusion injury by regulating iron metabolism","volume":"203","author":"Luo","year":"2023","journal-title":"Brain Res Bull"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"111005","DOI":"10.1016\/j.brainresbull.2024.111005","article-title":"Amentoflavone attenuates homocysteine-induced neuronal ferroptosis-mediated inflammatory response: involvement of the SLC7A11\/GPX4 axis activation","volume":"215","author":"Wang","year":"2024","journal-title":"Brain Res Bull"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"NP1","DOI":"10.1177\/0271678X19884443","article-title":"Ferrostatin-1 and deferoxamine as inhibitors of ferroptosis in cerebral ischemia: preclinical evidence","volume":"39","author":"Liu","year":"2019","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s12974-019-1516-2","article-title":"Neuroinflammation: friend and foe for ischemic stroke","volume":"16","author":"Jayaraj","year":"2019","journal-title":"J Neuroinflammation"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu Rev Immunol"},{"key":"ref71","first-page":"766","article-title":"Repulsive guidance molecule-a dictates the phenotypic fate of astrocyte and microglia after ischemic stroke via distinct mechanisms","volume":"14","author":"Zhang","year":"2023","journal-title":"Cell Death Dis"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"2280","DOI":"10.1177\/0271678X21995694","article-title":"Change and predictive ability of circulating immunoregulatory lymphocytes in long-term outcomes of acute ischemic stroke","volume":"41","author":"Li","year":"2021","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41582-018-0126-4","article-title":"Exosomes - beyond stem cells for restorative therapy in stroke","volume":"15","author":"Zhang","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"ref74","first-page":"15333175211044824","article-title":"The expression of circadian genes and proteins in different brain regions of elderly depression patients","volume":"36","author":"Wang","year":"2021","journal-title":"Am J Alzheimers Dis Other Dement"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1007\/s12264-019-00388-3","article-title":"Dual functions of microglia in ischemic stroke","volume":"35","author":"Qin","year":"2019","journal-title":"Neurosci Bull"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1172\/JCI135530","article-title":"Immune responses to stroke: mechanisms, modulation, and therapeutic potential","volume":"130","author":"Iadecola","year":"2020","journal-title":"J Clin Invest"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"456","DOI":"10.14336\/AD.2026.0803","article-title":"Single-cell RNA sequencing characterizes microglial phenotypic heterogeneity across different stroke subtypes","volume":"17","author":"Guo","year":"2026","journal-title":"Aging Dis"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"1234567","DOI":"10.3389\/fneur.2026.1789863","article-title":"Single-cell RNA sequencing reveals microglial proliferative bias and neuroinflammatory communication reprogramming following traumatic brain injury","volume":"17","author":"Zhang","year":"2026","journal-title":"Front Neurol"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.bbi.2023.10.022","article-title":"Gasdermin D activation in oligodendrocytes and microglia drives inflammatory demyelination in progressive multiple sclerosis","volume":"115","author":"Pollock","year":"2024","journal-title":"Brain Behav Immun"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"394","DOI":"10.25259\/SNI_703_2024","article-title":"Unveiling the hidden culprit: how the brain-gut axis fuels neuroinflammation in ischemic stroke","volume":"15","author":"Ma","year":"2024","journal-title":"Surg Neurol Int"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"119202","DOI":"10.1016\/j.ecoenv.2025.119202","article-title":"Exercise protects against PM2.5 exacerbated cerebral ischemia\/reperfusion injury via the gut-brain axis in mice","volume":"305","author":"Sun","year":"2025","journal-title":"Ecotoxicol Environ Saf"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"1234567","DOI":"10.3389\/fphar.2022.862204","article-title":"AMPK activation alleviates myocardial ischemia-reperfusion injury by regulating Drp1-mediated mitochondrial dynamics","volume":"13","author":"Du","year":"2022","journal-title":"Oxidative Med Cell Longev"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"4261","DOI":"10.1007\/s12035-023-03336-5","article-title":"Irisin attenuates apoptosis following ischemia-reperfusion injury through improved mitochondria dynamics and ROS suppression mediated through the PI3K\/Akt\/mTOR axis","volume":"60","author":"Liu","year":"2023","journal-title":"Mol Neurobiol"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.freeradbiomed.2025.01.031","article-title":"Naotaifang formula regulates Drp1-induced remodeling of mitochondrial dynamics following cerebral ischemia-reperfusion injury","volume":"229","author":"She","year":"2025","journal-title":"Free Radic Biol Med"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s12192-022-01273-1","article-title":"The mitochondria-targeted antioxidant MitoQ ameliorates myocardial ischemia-reperfusion injury by enhancing PINK1\/parkin-mediated mitophagy in type 2 diabetic rats","volume":"27","author":"Ji","year":"2022","journal-title":"Cell Stress Chaperones"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1080\/02656736.2018.1536285","article-title":"Heat shock protein expression and autophagy after incomplete thermal ablation and their correlation","volume":"36","author":"Chen","year":"2019","journal-title":"Int J Hyperth"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"567","DOI":"10.2174\/011570159X433721260101212425","article-title":"Reviving brain waste clearance: a pharmacological perspective on glymphatic dysfunction and AQP4 modulation","volume":"24","author":"Banerjee","year":"2026","journal-title":"Curr Neuropharmacol"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3390\/ijms26093949","article-title":"Spatial omics in clinical research: a comprehensive review of technologies and guidelines","volume":"26","author":"Lee","year":"2025","journal-title":"Int J Mol Sci"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/978-1-0716-4298-6_20","article-title":"Proteomics-based analysis of laser-capture micro-dissected, formalin-fixed paraffin-embedded tissue samples","volume":"2884","author":"Maia","year":"2025","journal-title":"Methods Mol Biol"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"111584","DOI":"10.1016\/j.brainresbull.2025.111584","article-title":"The role of VCAM1 in post-stroke cognitive impairment: molecular mechanisms and therapeutic potential","volume":"232","author":"Zhang","year":"2025","journal-title":"Brain Res Bull"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"2692","DOI":"10.1038\/s41467-023-38360-5","article-title":"Spatially resolved multi-omics highlights cell-specific metabolic remodeling and interactions in gastric cancer","volume":"14","author":"Sun","year":"2023","journal-title":"Nat Commun"},{"key":"ref92","doi-asserted-by":"publisher","DOI":"10.1101\/2023.09.24.559173","article-title":"Spatial-live: a lightweight and versatile tool for single cell spatial-omics data visualization","author":"Ye","year":"2023","journal-title":"bioRxiv"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1038\/s41592-025-02651-0","article-title":"scMultiSim: simulation of single-cell multi-omics and spatial data guided by gene regulatory networks","volume":"22","author":"Li","year":"2025","journal-title":"Nat Methods"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.3390\/brainsci13071007","article-title":"Animal models of ischemic stroke with different forms of middle cerebral artery occlusion","volume":"13","author":"Zeng","year":"2023","journal-title":"Brain Sci"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"1234567","DOI":"10.3389\/fgene.2023.1169190","article-title":"Identification of the lncRNA-miRNA-mRNA regulatory network for middle cerebral artery occlusion-induced ischemic stroke","volume":"14","author":"Shi","year":"2023","journal-title":"Front Genet"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"2024.04.04.588110","DOI":"10.1101\/2024.04.04.588110","article-title":"Three-photon excited fluorescence microscopy enables imaging of blood flow, neural structure and inflammatory response deep into mouse spinal cord in vivo","author":"Cheng","year":"2024","journal-title":"bioRxiv [Preprint]"},{"key":"ref97","article-title":"Sliding window functional connectivity inference with nonstationary autocorrelations","author":"Zhang","year":"2024","journal-title":"bioRxiv"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1038\/s41467-022-29992-0","article-title":"Selective plasticity of callosal neurons in the adult contralesional cortex following murine traumatic brain injury","volume":"13","author":"Empl","year":"2023","journal-title":"Nat Commun"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1038\/s41593-023-01405-5","article-title":"Prominent in vivo influence of single interneurons in the developing barrel cortex","volume":"26","author":"Bollmann","year":"2023","journal-title":"Nat Neurosci"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"3895","DOI":"10.1038\/s41598-018-22193-0","article-title":"PDE4D regulates spine plasticity and memory in the retrosplenial cortex","volume":"8","author":"Baumg\u00e4rtel","year":"2018","journal-title":"Sci Rep"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1007\/s11011-024-01410-y","article-title":"Morin attenuated the global cerebral ischemia via antioxidant, anti-inflammatory, and antiapoptotic mechanisms in rats","volume":"39","author":"Alla","year":"2024","journal-title":"Metab Brain Dis"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s13205-023-03854-y","article-title":"Tangeretin confers neuroprotection, cognitive and memory enhancement in global cerebral ischemia","volume":"14","author":"Alla","year":"2024","journal-title":"3 Biotech"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"155326","DOI":"10.1016\/j.phymed.2023.155326","article-title":"Salvianolic acid a provides neuroprotective effects on cerebral ischemia-reperfusion injury via PKA\/CREB\/c-Fos signaling pathway","volume":"124","author":"Yang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"102886","DOI":"10.1016\/j.tice.2025.102886","article-title":"Bavachinin attenuates cerebral ischemia\/reperfusion injury via its anti-inflammatory and antioxidant effects","volume":"95","author":"Atlasbaf","year":"2025","journal-title":"Tissue Cell"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"8818328","DOI":"10.1155\/2020\/8818328","article-title":"Electroacupuncture on trigeminal nerve-innervated acupoints ameliorates poststroke cognitive impairment","volume":"2020","author":"Zheng","year":"2020","journal-title":"Neural Plast"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000548456","article-title":"Circadian rhythms in ischemic stroke: from molecular pathways to chronotherapeutic strategies","author":"Deb","year":"2025","journal-title":"Eur Neurol"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"e70704","DOI":"10.1002\/alz.70704","article-title":"A phase 2A\/B randomized trial of metabolic modulators for MCI and early AD","volume":"21","author":"Erichsen","year":"2025","journal-title":"Alzheimers Dement"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"627682","DOI":"10.3389\/fncel.2021.627682","article-title":"Glial cell-based vascular mechanisms and transplantation therapies","volume":"15","author":"Zhao","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"569","DOI":"10.19540\/j.cnki.cjcmm.20221019.601","article-title":"Regulation of ischemic stroke by circadian rhythm and intervention by traditional Chinese medicine","volume":"48","author":"Li","year":"2023","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref110","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.3233\/JAD-230886","article-title":"Communication regarding myocardial ischemia\/reperfusion and cognitive impairment","volume":"97","author":"Chang","year":"2024","journal-title":"J Alzheimer's Dis"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1002\/cbf.2914","article-title":"Synaptic localization of growth-associated protein 43 in cultured hippocampal neurons during synaptogenesis","volume":"31","author":"Morita","year":"2012","journal-title":"Cell Biochem Funct"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41531-020-00147-6","article-title":"Plasma-borne indicators of inflammasome activity in Parkinson\u2019s disease patients","volume":"7","author":"Anderson","year":"2021","journal-title":"NPJ Parkinsons Dis"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"8123","DOI":"10.3390\/ijms22062951","article-title":"Proteomics profiling of neuron-derived small extracellular vesicles from human plasma: enabling single-subject analysis","volume":"22","author":"Anastasi","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"157508","DOI":"10.1016\/j.phymed.2025.157508","article-title":"Dalbergia odorifera leaf extract promotes microglial energy expenditure after cerebral ischemia-reperfusion","volume":"149","author":"Wu","year":"2025","journal-title":"Phytomedicine"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s42466-024-00355-y","article-title":"Ischemia\/reperfusion injury in acute human and experimental stroke","volume":"6","author":"Stoll","year":"2024","journal-title":"Neurol Res Pract"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"e5244","DOI":"10.21769\/BioProtoc.5244","article-title":"Developing a ministroke model in mouse barrel cortex","volume":"15","author":"Wang","year":"2025","journal-title":"Bio Protoc"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"117873","DOI":"10.1016\/j.ejmech.2025.117873","article-title":"Discovery of a potential anti-ischemic stroke agent by suppressing ferroptosis","volume":"296","author":"Kong","year":"2025","journal-title":"Eur J Med Chem"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"5424","DOI":"10.1007\/s12010-022-04060-x","article-title":"Cynaropicrin averts oxidative stress and neuroinflammation in ischemic\/reperfusion injury","volume":"195","author":"Jin","year":"2023","journal-title":"Appl Biochem Biotechnol"},{"key":"ref119","doi-asserted-by":"publisher","first-page":"6200","DOI":"10.1007\/s12035-023-03909-4","article-title":"Exploring research trend on oxidative stress in ischemic stroke","volume":"61","author":"Jiang","year":"2022","journal-title":"Mol Neurobiol"},{"key":"ref120","doi-asserted-by":"publisher","DOI":"10.23812\/21-SI1-8","article-title":"LINC00665 knockdown protects against cerebral ischemia-reperfusion injury","volume":"35","author":"Yan","year":"2021","journal-title":"J Biol Regul Homeost Agents"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"1613464","DOI":"10.3389\/fphar.2025.1613464","article-title":"Cerebral ischemia-reperfusion injury: mechanisms and promising therapies","volume":"16","author":"Yang","year":"2025","journal-title":"Front Pharmacol"},{"key":"ref122","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.13345\/j.cjb.240605","article-title":"Machine learning-aided design of synthetic biological parts and circuits [article in Chinese]","volume":"41","author":"Mao","year":"2025","journal-title":"Sheng Wu Gong Cheng Xue Bao"},{"key":"ref123","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1007\/978-1-0716-4690-8_26","article-title":"Review on advancement of AI in synthetic biology","volume":"2952","author":"Mirchandani","year":"2025","journal-title":"Methods Mol Biol"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/978-1-0716-4690-8_6","article-title":"Advancements in AI for computational biology","volume":"2952","author":"Nalina","year":"2025","journal-title":"Methods Mol Biol"},{"key":"ref125","doi-asserted-by":"publisher","first-page":"105432","DOI":"10.1016\/j.neuint.2022.105432","article-title":"MMP-12 knockdown prevents secondary brain damage after ischemic stroke","volume":"161","author":"Arruri","year":"2022","journal-title":"Neurochem Int"},{"key":"ref126","doi-asserted-by":"publisher","first-page":"2244","DOI":"10.1007\/s11064-022-03610-3","article-title":"Acute treatment with nicotinamide riboside chloride reduces hippocampal damage and preserves the cognitive function of mice with ischemic injury","volume":"47","author":"Cheng","year":"2022","journal-title":"Neurochem Res"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"9636897211041585","DOI":"10.1177\/09636897211041585","article-title":"Delta opioid receptor activation improves synaptic remodeling","volume":"30","author":"Zhang","year":"2021","journal-title":"Cell Transplant"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"125329","DOI":"10.1016\/j.jstrokecerebrovasdis.2024.108000","article-title":"Activating PKA signaling regulates Cx43 expression","volume":"33","author":"Chen","year":"2024","journal-title":"J Stroke Cerebrovasc Dis"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1912737\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:41:01Z","timestamp":1790070061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1912737\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":128,"alternative-id":["10.3389\/fneur.2026.1912737"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1912737","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1912737"}}